C F Lippa1, M L Schmidt, V M Lee, J Q Trojanowski. 1. Department of Neurology, Medical College of Pennsylvania--Hahnemann University, 3300 Henry Ave, Philadelphia, PA 19129, USA. carol.lippa@drexel.edu
Abstract
BACKGROUND: Alpha-synuclein is a major component of Lewy bodies (LBs) in Parkinson disease and dementia with LBs and of glial cytoplasmic inclusions in multiple system atrophy. However, epitope mapping for alpha-synuclein is distinctive in different neurodegenerative diseases. The reasons for this are poorly understood but may reflect fundamental differences in disease mechanisms. OBJECTIVE: To investigate the alpha-synuclein epitope mapping properties of LBs in familial Alzheimer disease. DESIGN AND SETTING: We compared LBs in familial Alzheimer disease with those in synucleinopathies by probing 6 brains of persons with familial Alzheimer disease using a panel of antibodies to epitopes spanning the alpha-synuclein protein. Results were compared with data from brains of persons with Parkinson disease, dementia with LBs, and multiple system atrophy. RESULTS: The brains of persons with familial Alzheimer disease showed consistent staining of LBs with all antibodies, similar to Parkinson disease and dementia with LBs but different from alpha-synuclein aggregates that occurred in multiple system atrophy. CONCLUSIONS: These data suggest that the epitope profiles of alpha-synuclein in LBs are similar, regardless of whether the biological trigger is related to synuclein or a different genetic pathway. These findings support the hypothesis that the mechanism of alpha-synuclein aggregation is the same within cell types but distinctive between cell types.
BACKGROUND:Alpha-synuclein is a major component of Lewy bodies (LBs) in Parkinson disease and dementia with LBs and of glial cytoplasmic inclusions in multiple system atrophy. However, epitope mapping for alpha-synuclein is distinctive in different neurodegenerative diseases. The reasons for this are poorly understood but may reflect fundamental differences in disease mechanisms. OBJECTIVE: To investigate the alpha-synuclein epitope mapping properties of LBs in familial Alzheimer disease. DESIGN AND SETTING: We compared LBs in familial Alzheimer disease with those in synucleinopathies by probing 6 brains of persons with familial Alzheimer disease using a panel of antibodies to epitopes spanning the alpha-synuclein protein. Results were compared with data from brains of persons with Parkinson disease, dementia with LBs, and multiple system atrophy. RESULTS: The brains of persons with familial Alzheimer disease showed consistent staining of LBs with all antibodies, similar to Parkinson disease and dementia with LBs but different from alpha-synuclein aggregates that occurred in multiple system atrophy. CONCLUSIONS: These data suggest that the epitope profiles of alpha-synuclein in LBs are similar, regardless of whether the biological trigger is related to synuclein or a different genetic pathway. These findings support the hypothesis that the mechanism of alpha-synuclein aggregation is the same within cell types but distinctive between cell types.
Authors: Jozsef Gal; Jing Chen; Yuriko Katsumata; David W Fardo; Wang-Xia Wang; Sergey Artiushin; Douglas Price; Sonya Anderson; Ela Patel; Haining Zhu; Peter T Nelson Journal: J Neuropathol Exp Neurol Date: 2018-01-01 Impact factor: 3.685
Authors: Peter T Nelson; Erin L Abner; Ela Patel; Sonya Anderson; Donna M Wilcock; Richard J Kryscio; Linda J Van Eldik; Gregory A Jicha; Zsombor Gal; Ruth S Nelson; Bela G Nelson; Jozsef Gal; Md Tofial Azam; David W Fardo; Matthew D Cykowski Journal: J Neuropathol Exp Neurol Date: 2018-01-01 Impact factor: 3.685
Authors: Yi-Ju Li; William K Scott; Dale J Hedges; Fengyu Zhang; P Craig Gaskell; Martha A Nance; Ray L Watts; Jean P Hubble; William C Koller; Rajesh Pahwa; Matthew B Stern; Bradley C Hiner; Joseph Jankovic; Fred A Allen; Christopher G Goetz; Frank Mastaglia; Jeffrey M Stajich; Rachel A Gibson; Lefkos T Middleton; Ann M Saunders; Burton L Scott; Gary W Small; Kristin K Nicodemus; Allison D Reed; Donald E Schmechel; Kathleen A Welsh-Bohmer; P Michael Conneally; Allen D Roses; John R Gilbert; Jeffery M Vance; Jonathan L Haines; Margaret A Pericak-Vance Journal: Am J Hum Genet Date: 2002-03-01 Impact factor: 11.025